{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:32:07Z","timestamp":1790886727272,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bacillus Calmette-Gu\u00e9rin (BCG), an attenuated strain of <jats:italic>Mycobacterium bovis (M. bovis)<\/jats:italic>, is the lead candidate vaccine for control of bovine tuberculosis (TB) in cattle. However, BCG vaccination sensitises cattle to bovine tuberculin, thus compromising the use of the current bovine TB surveillance tests. To address this, we have developed a diagnostic skin test that is not compromised by BCG vaccination and is able to detect BCG vaccinated animals that subsequently develop bovine TB following exposure to <jats:italic>M. bovis<\/jats:italic>. Building on previous work using \u2018in house\u2019 formulated protein cocktail reagents, we herein present test performance data for a single fusion protein (DST-F) containing the mycobacterial antigens ESAT-6, CFP-10 and Rv3615c formulated as a \u2018ready to use\u2019 reagent by a commercial manufacturer. Our results demonstrate that, unlike tuberculin reagents, a diagnostic skin test using DST-F maintained high specificity in BCG vaccinated animals. Furthermore, the DST-F skin test demonstrated a high relative sensitivity in identifying <jats:italic>M. bovis<\/jats:italic> infected animals, including those where BCG vaccination failed to prevent bovine TB pathology following experimental exposure to <jats:italic>M. bovis<\/jats:italic>. The DST-F is currently undergoing field trials in Great Britain to support its licensure and commercialisation.<\/jats:p>","DOI":"10.1038\/s41598-022-16092-8","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T16:03:09Z","timestamp":1657814589000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Test performance data demonstrates utility of a cattle DIVA skin test reagent (DST-F) compatible with BCG vaccination"],"prefix":"10.1038","volume":"12","author":[{"given":"Gareth J.","family":"Jones","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timm","family":"Konold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shellene","family":"Hurley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Holder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Steinbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mick","family":"Coad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-8641","authenticated-orcid":false,"given":"D.","family":"Neil Wedlock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce M.","family":"Buddle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahavir","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Martin Vordermeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"16092_CR1","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1016\/j.vaccine.2012.02.018","volume":"30","author":"WR Waters","year":"2012","unstructured":"Waters, W. R., Palmer, M. V., Buddle, B. M. & Vordermeier, H. M. Bovine tuberculosis vaccine research: Historical perspectives and recent advances. Vaccine 30, 2611\u20132622. https:\/\/doi.org\/10.1016\/j.vaccine.2012.02.018 (2012).","journal-title":"Vaccine"},{"key":"16092_CR2","doi-asserted-by":"publisher","first-page":"325","DOI":"10.20506\/rst.20.1.1266","volume":"20","author":"DA Ashford","year":"2001","unstructured":"Ashford, D. A., Whitney, E., Raghunathan, P. & Cosivi, O. Epidemiology of selected mycobacteria that infect humans and other animals. Rev. Sci. Tech. 20, 325\u2013337. https:\/\/doi.org\/10.20506\/rst.20.1.1266 (2001).","journal-title":"Rev. Sci. Tech."},{"key":"16092_CR3","unstructured":"Godfray, C., Donnelly, C., Hewinson, G., Winter, M. & Wood, J. (ed DEFRA) (London, UK, 2018)."},{"key":"16092_CR4","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3389\/fvets.2018.00259","volume":"5","author":"BM Buddle","year":"2018","unstructured":"Buddle, B. M., Vordermeier, H. 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Field evaluation of the protective efficacy of Mycobacterium bovis BCG vaccine against bovine tuberculosis. Res. Vet. Sci. 88, 44\u201349. https:\/\/doi.org\/10.1016\/j.rvsc.2009.05.022 (2010).","journal-title":"Res. Vet. Sci."},{"key":"16092_CR7","doi-asserted-by":"publisher","first-page":"7338","DOI":"10.1016\/j.vaccine.2018.10.025","volume":"36","author":"G Nugent","year":"2018","unstructured":"Nugent, G., Yockney, I. J., Cross, M. L. & Buddle, B. M. Low-dose BCG vaccination protects free-ranging cattle against naturally-acquired bovine tuberculosis. Vaccine 36, 7338\u20137344. https:\/\/doi.org\/10.1016\/j.vaccine.2018.10.025 (2018).","journal-title":"Vaccine"},{"key":"16092_CR8","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.vetmic.2017.07.029","volume":"208","author":"G Nugent","year":"2017","unstructured":"Nugent, G., Yockney, I. J., Whitford, J., Aldwell, F. E. & Buddle, B. M. 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Immun."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-16092-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-16092-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-16092-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T04:33:20Z","timestamp":1669350800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-16092-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["16092"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-16092-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]},"assertion":[{"value":"9 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"H.M.V., G.J.J, T.K., S.H., T.H., S.S. and M.C. are employed by the Animal and Plant Health Agency (APHA) who holds 3 patents for the use of Rv3615c in diagnostic tests for bovine TB (WO\/2009\/060184, WO\/2011\/135369 and WO\/2012\/010875). The work at APHA has been funded by the GB bovine TB research budget held and administered centrally by Defra on behalf of England, Scotland and Wales. M.S. is the owner of Lionex GmBH and owns stock in the company. The remaining authors (D.N.W. and B.M.B.) declare no potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12052"}}